journal article·2026-04Open access

Substantially Altered Local and Systemic Immunity in Ischemia‐Free Versus Conventional Liver Transplantation

Tao Luo, Shuai He, Shirui Chen, Dongmei Ye, Shibo Zhang, Di Liu, Dawei Zou, Linhe Wang, Huadi Chen, Jinghong Xu, Huanjie Liu, Ruiting Liu, Xi Tan, Yitong Wang, Jiayi Zeng, Runbing Mo, Yuexin Li, Yuyi Zhang, Tanyiyang Ruan, Tielong Wang, Zehua Jia, Yu Jia, Tongdi Fang, Yimou Lin, Xiaorui Liu, Yunhua Tang, Maogen Chen, Qiang Zhao, Anbin Hu, Weiqiang Ju, Yi Ma, Dongping Wang, Xiaofeng Zhu, Schlegel Andrea, Yuan Zhai, Kwan Man, Tullius G. Stefan, Yifang Gao, Jinxin Bei, Xiaoshun He, Zhiyong Guo

Advanced Science· Volume 13· Issue 23

Abstract

ABSTRACT Ischemia‐free liver transplant (IFLT) has been developed to reduce ischemia‐reperfusion injury (IRI). This study aims to investigate how this procedure impacts local and systemic immunity compared to conventional liver transplantation (CLT). Immunohistochemistry, immunofluorescence staining, single‐cell RNA sequencing (scRNA‐seq), and multiplex cytokine are used to illustrate distinct local and systemic immunity. In contrast to CLT, IFLT reduces neutrophil infiltration and neutrophil extracellular trap formation in grafts. By constructing an immune cell chimerism atlas, we reveal that IFLT reduces recipient‐derived monocyte infiltration by suppressing ANXA1‐FPR1 signaling through the STAT3‐HIF‐1α pathway, thereby attenuating inflammatory responses in graft monocytes. Additionally, IFLT confers graft protection by upregulating HMOX1 expression in monocytes and macrophages. Peripherally, IFLT significantly reduces the expression of MHC II molecules in circulating monocytes. Accordingly, CD8 + effector T cell composition, T helper 1 (Th1) and Th17 cytokine levels are reduced, while regulatory T cell (Treg) composition and Th2 cytokine levels are increased in IFLT versus CLT recipients. These results show that IFLT profoundly affects local and systemic immunity in liver transplantation. Recipient‐circulating monocytes might play a key role in the interaction between graft IRI and allograft rejection.
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Research context

OpenAlex topics: Organ Transplantation Techniques and Outcomes · Liver Disease and Transplantation · Neutrophil, Myeloperoxidase and Oxidative Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Organ Transplant Center The First Affiliated Hospital Sun Yat‐sen University Guangzhou China

Guangdong Provincial Key Laboratory of Organ Medicine Guangzhou China

Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) Guangzhou China

NHC Key Laboratory of Assisted Circulation Sun Yat‐sen University Guangzhou China

State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou China

Immunobiology & Transplant Science Center Department of Surgery Houston Methodist Hospital Houston Methodist Research Institute Houston USA

Transplantation Center Digestive Disease and Surgery Institute, and Department of Immunology Cleveland Clinic Lerner Research Institute Cleveland USA

Transplant Surgery College of Medicine Medical University of South Carolina Charleston South Carolina USA

Department of Surgery HKU‐Shenzhen Hospital & Department of Surgery LKS Faculty of Medicine The University of Hong Kong Hong Kong China

Division of Transplant Surgery Department of Surgery Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

Funding

Natural Science Foundation of Guangdong Province · National Natural Science Foundation of China

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